Methods of forming large arrays of oligonucleotides, peptides and other polymers on a solid substrate are known. Pirrung et al., U.S. Pat. No. 5,143,854 (see also PCT Application No. WO 90/15070), McGall et al., U.S. Ser. No. 06/440742, Chee et al., SN PCT/US94/12305, and Fodor et al., PCT Publication No. WO 92/10092 describe methods of forming vast arrays of peptides, oligonucleotides and other polymers using, for example, light-directed synthesis techniques.
In the Fodor et al. PCT application, methods are described for using computer-controlled systems to direct polymer array synthesis. Using the Fodor approach, one heterogeneous array of polymers is converted, through simultaneous coupling at multiple reaction sites, into a different heterogeneous array. See also, U.S. Ser. No. 07/796,243 and U.S. Ser. No. 07/980,523 and Fodor et al. (1991) Science, 251: 767–777.
The arrays are typically placed on a solid surface with an area less than 1 inch2, although much larger surfaces are optionally used.
More recently, U.S. applications U.S. Ser. No. 06/440,742, U.S. Ser. No. 08/284,064, U.S. Ser. No. 08/143,312, U.S. Ser. No. 08/082,937 and PCT application (designating the United States) SN PCT/U594/12305, describe methods of making arrays of oligonucleotide and oligonucleotide analogue probes, e.g., to check or determine a partial or complete sequence of a target nucleic acid, or to detect the presence of a nucleic acid containing a specific oligonucleotide sequence. U.S. application Ser. No. 08/327,687 and U.S. application Ser. No. 06/440,742 describe methods of creating libraries of nucleic acid probes for the analysis of nucleic acid hybridization, and for screening nucleic acid binding molecules, e.g., as potential therapeutic agents.
Additional methods applicable to polymer synthesis on a substrate are described in co-pending Applications U.S. Ser. No. 07/980,523, filed Nov. 20, 1992, and U.S. Ser. No. 07/796,243, filed Nov. 22, 1991, incorporated herein by reference for all purposes. In the methods disclosed in these applications, reagents are delivered to the substrate by flowing or spotting polymer synthesis reagents on predefined regions of the solid substrate. In each instance, certain activated regions of the substrate are physically separated from other regions when the monomer solutions are delivered to the various reaction sites, e.g., by means of grooves, wells and the like.